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- Received August 9, 1996
- Revision received June 9, 1997
- Accepted June 26, 1997
- Published online October 1, 1997.
- ↵*Dr. Anwer Dhala, Cardiology Clinic, Children’s Hospital of Wisconsin, 8701 Watertown Plank Road, Mail Station 713, Milwaukee, Wisconsin 53226.
Objectives. This study sought to determine the specificity of commonly used tilt protocols in children.
Background. Tilt table testing is commonly utilized in the evaluation of children and adolescents with syncope despite a lack of uniformity in tilt protocols and a lack of studies of specificity in normal control subjects.
Methods. Sixty-nine normal control volunteers (12 to 18 years old, 38 male, 31 female) with no previous history of syncope, presyncope or arrhythmia underwent tilting to 80°, 70° or 60° for a maximum of 30 min on a motorized table with a footboard support. Autonomic maneuvers, including deep breathing, carotid massage, Valsalva maneuver and diving reflex, were performed before tilt testing to determine whether the response to these maneuvers could identify subjects prone to fainting during tilt testing.
Results. Symptoms of presyncope and frank syncope were elicited in 24 of 69 subjects (13 male, 11 female): 6 (60%) of 10 were tilted at 80°, 9 (29%) of 31 at 70° and 9 (32%) of 28 at 60°. Tilt testing at 80° was terminated after the tenth subject by the institutional review board. The mean time to a positive test response was 10.5 min at 80°, 14.2 min at 70° and 13.2 min at 60°. In the 80° tilt, 4 of 10 subjects had a positive response within 10 minutes, whereas only 3 of 31 and 2 of 28 had a positive response within <10 min at 70° and 60° tilt angles, respectively. Subjects with and without a positive response to tilt testing were similar with respect to age; gender; PR, QRS and QT intervals; and baseline heart rate and blood pressure. Likewise, responses to other autonomic function tests performed were similar in tilt-positive and tilt-negative patients. The power for detecting a significant difference between patients tilted at 80° versus 60° and 70° was 0.45 and for detecting differences in autonomic tone between tilt-positive (n = 24) and tilt-negative (n = 45) subjects was 0.8.
Conclusions. Children appear to be more susceptible to orthostatic stress than adults. Therefore, tilt protocols commonly used in adults lack specificity in teenage patients. A specificity >85% may be obtained by performing the tilt test at 60° or 70° for no longer than 10 min.
Syncope is a common and anxiety-provoking event that occurs at all ages but may be particularly common in adolescence. Syncope was the chief complaint for 1% of all emergency room admissions in a pediatric study , and at least 15% of all children will experience a syncopal episode before the end of the second decade [2–4]. Except for the few patients with structural heart disease, the most likely etiology is neurocardiogenic or vasovagal syncope. Syncope or presyncopal symptoms frequently occur under fairly typical circumstances, such as during prolonged standing in warm and crowded surroundings or in association with noxious stimuli (e.g., while having blood drawn) and are preceded by prodromata, such as lightheadedness and nausea. However, in a not insignificant minority of subjects, presentation may be atypical, as in an abrupt onset of syncope with no clear triggers. Under these circumstances, although neurocardiogenic syncope remains the most common etiology, the need for a test with high specificity is obvious. The head-up tilt test is being increasingly used in the workup of the child or adolescent with syncope [5–8], and if it can reliably identify neurocardiogenic syncope, it can supplant the extensive and expensive investigations that are often performed in such patients . Tilt table studies in normal adult control subjects have shown a low incidence of positive responses [10–12].
Few studies characterizing heart rate, blood pressure or electrocardiographic (ECG) responses in normal children and adolescents exist for comparison despite their being the most frequently affected population . Additionally, reported tilt protocols vary in terms of the tilt angle used, duration in the upright position, intravascular instrumentation and the use of isoproterenol as a provocative maneuver . The specificity of the head-up tilt test is known to be influenced by these variables. By performing the head-up tilt test at different tilt angles in healthy adolescents, the aim of the present study, therefore, was to determine a tilt protocol that could provide a degree of specificity that would make the test clinically useful.
1.1 Study patients.
Sixty-nine healthy volunteers (12 to 18 years old) with no previous history of syncope, presyncope, acquired or congenital cardiac disease, palpitations, or chest pains or currently using any medications were enrolled in the study. Informed consent was obtained from both the subjects and a parent.
1.2 Autonomic function testing.
Testing was performed in the postabsorbtive state, 4 h after the last meal. All subjects were placed supine on an electronic tilt table and were attached to an ECG monitor (Marquette Sentra, Marquette Electronics) and an automated blood pressure cuff (Suntech). A baseline ECG was obtained along with blood pressure. After application of EMLA cream to intravenous line sites, a 20- to 22-gauge intravenous catheter was placed, and a normal saline infusion was begun at 50 ml/h. After a 10-min rest period to return to baseline, the autonomic function tests were begun. With continuous ECG monitoring, slow deep breathing was performed for 1 min. After a brief rest, right and then left carotid massage for 10 s was performed. After another rest period, a Valsalva maneuver was performed for 30 s. The final autonomic challenge was the diving reflex elicited by application of an ice-cold towel to the subject’s face for 30 s. During each maneuver, the shortest and longest RR intervals were measured, and blood pressure was measured after 30 s of each autonomic challenge.
1.3 Tilt protocol.
After another brief rest period, the subjects were tilted upright to the desired tilt angle (60°, 70° or 80°) for 30 min or until symptoms were encountered. The first 10 subjects were tilted at 80°, and the subsequent 59 were randomized to either 60° or 70° tilt. Heart rate and rhythm were continuously recorded, and blood pressure was measured every 2 min plus whenever symptoms ensued. At the end of the 30 min or at the appearance of symptoms, the tilt table was returned to the supine position and the test concluded. A positive head-up tilt test responsewas defined as one in which hypotension with or without bradycardia was found to be sufficiently severe to have caused syncope or presyncope.
1.4 Data analysis.
Continuous variables are presented as mean value ± SD, and the Mann-Whitney or Wilcoxon rank sum test was used for comparisons when not normally distributed. Categoric variables are presented as frequencies, and the Fischer exact test was used for comparisons. The power of the study to detect differences in response to 80° tilt compared with other tilt angles, as well as differences in response to autonomic function tests between tilt-positive and tilt-negative subjects, was calculated. A p value <0.05 was considered statistically significant. As a validity measure, the specificity of the test was also calculated.
A total of 69 subjects (34 male, 35 female) underwent testing. The first 10 subjects (mean [±SD] age 15.1 ± 1.7 [SE 0.5]) were tilted at 80°. Of these 10, 6 had a positive test response, including 1 with prolonged asystole. At the recommendation of our institutional review committee, further testing at this tilt angle was not performed. The remaining 59 subjects were randomized to tilting either at 60° (28 subjects, mean age 14.3 ± 1.6 [SE 0.3]) or 70° (31 subjects, mean age 14.8 ± 1.8 [SE 0.3]).
2.2 Head-up tilt results.
Results of the head-up tilt test are summarized in Table 1. Overall, 24 subjects (35%) developed a positive response during the test. The incidence of positive responses was highest in subjects tilted at 80° (60%) but was similar in those tilted at 60° and 70° (32% vs. 29%, respectively). However, the difference between 80° and other tilt angles did not reach statistical significance (p = 0.085), probably because too few subjects were tilted at 80°, giving a statistical power of 0.45. At least 20 subjects would have been required to be tilted at 80° to demonstrate a statistically significant difference (12 of 20 vs. 18 of 59, p value 0.032). The mean time to a positive tilt response was also shorter at 80° (10.5 min) than at 70° and 60° (14.2 and 13.2 min, respectively). Accordingly, the specificity of the head-up tilt test was 40%, 71% and 69% at 80°, 70° and 60°, respectively when subjects were tilted up to 30 min. If a maximum of 10 min in the upright position had been utilized, there would have still been a positive response of 40% (4 of 10) at the 80° tilt angle compared with 10% (3 of 31) and 7% (2 of 28) at 70° and 60°, respectively.
Table 2compares baseline demographics and heart rate and blood pressure responses at baseline and after the various autonomic tests in patients with and without a positive head-up tilt test response. As expected, the minimal heart rate and blood pressure were significantly lower during a positive tilt test response but responses to other autonomic tests were not different in the two groups, as shown in Table 3. The power of the present study to show a clinically meaningful difference in the variables shown in Table 3was 0.8 for these data.
In the present study we found the specificity of head-up tilt testing in adolescents to be much lower than that reported for adults. We terminated tilt testing at 80° because 6 of the 10 subjects tested at this angle had a positive response, including 1 with prolonged asystole. Moreover, four subjects were test positive within 10 min of being in the upright position. A high false positive rate was also found at the 60° and 70° angles if tilting lasted for 30 min.
In the published reports, tilt angles usually range from 60° to 90° for 10 to 60 min, with or without isoproterenol provocation, if the baseline test response is negative. Such protocols in normal adult subjects result in a positive test response in none to 65% of subjects, depending on the degree of tilt and isoproterenol provocation. Natale et al. tested a large number of volunteers and found a specificity of 92% for tilt angles of 60° and 70° 80% for a tilt angle of 80° at a test duration of 20 min. Low dose isoproterenol did not adversely affect the specificity of the test, but in doses of 3 to 5 μg/min, the specificity was significantly reduced, similar to the findings of Kapoor and Brant . Few reports are available on tilt testing in control subjects of pediatric age and typically involve <25 subjects [5, 16, 17]. Again, a variety of test protocols were used, and a comparison between different protocols was not attempted. Although, the high false positive rate in the present study is at variance with some of these smaller pediatric control studies, in the only other study that utilized a large number of pediatric control subjects, Van Steenwijk et al. found that 29 (40%) of 68 of their normal subjects had false positive tests. These investigators attributed the high false positive response to the fact that frequent blood samples were drawn in the upright position, although the higher incidence compared with that of the present study may at least in part be due to the fact that the age distribution was much younger. Tilting during isoproterenol infusion was not performed in our study nor in that by Van Steenwijk et al. Perusal of published reports suggests that the incidence of false positive tests is likely to be even higher.
The present study raises serious issues regarding the applicability of using head-up tilt testing in the diagnosis of unexplained syncope in children. The incidence of neurocardiogenic syncope appears to be higher in children. It may therefore be argued that a “false positive” response in a subject probably does represent a true susceptibility to clinical neurocardiogenic syncope. However, even if this were true, it would still detract from the clinical value of the test because a significant proportion of adolescent patients are likely to have a positive response to tilt table testing regardless of the etiology of their clinical syncope.
Another variable that is potentially confounding during head-up tilt testing is the impact of intravascular instrumentation on the outcome of the test. Although such intervention may not be a significant factor during testing in adults, children in general manifest much greater levels of anxiety to such interventions. We attempted to minimize anxiety associated with placing the intravenous line by the application of topical lidocaine and a waiting period before autonomic testing to allow the heart rate to return to baseline levels. Again, from a clinical perspective, our results are probably relevant because intravenous lines are usually placed during clinical tilt table testing.
3.1 Clinical implications.
The present study suggests that a protocol of 60° or 70° tilt testing for no more than 10 min would provide a reasonable specificity. The sensitivity of such an abbreviated protocol is unknown but is likely to be lower because sensitivity is inversely related to specificity. Even with currently used protocols, 30% to 40% of patients with otherwise unexplained syncope have a negative head-up tilt test response.
Currently used tilt protocols lack specificity when used in children. Among the protocols tested, a 60° or 70° tilt for no more than 10 min may have adequate specificity.
- Received August 9, 1996.
- Revision received June 9, 1997.
- Accepted June 26, 1997.
- The American College of Cardiology
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